Process for the production of(+)-trans-chrysanthemic acid

ABSTRACT

1. A PROCESS FOR ISOLATION OF (+) TRANS-CHRYSANTHEMIC ACID WHICH COMPRISES DISSOLVING ($)-TRANS-CHRYSANTHEMIC ACID OR ($)-CIS, TRANS-CHRYSANTHEMIC ACID IN A SOLVENT SELECTED FRON THE GROUP CONSISTING OF WATER, LOWER ALKYL ALCOHOLS, LOWER ALKYL ETHERS, DIOXANE, TETRAHYDROFURAN, LOWER ALKYL KETONES AND A MIXTURE THEREOF, ADING (-)-A(1-NAPHTHYL)-ETHYLAMINE TO THE SOLUTION, COOLING THE RESULTING HOMOGENEOUS SOLUTION TO DEPOSIT CRYSTALS OF THE AMINE SALT OF (+)-TRANS-CHRYSANTHEMIC ACID, DECOMPOSING THE SALT BY AN ACID OR AN ALKALI, AND RECOVERRING (+)TRANS-CHRYSANTHEMIC ACID.

United States Patent 3,842,125 PROCESS FOR THE PRODUCTION OF(+)-TRANS-CHRYSANTHEMIC ACID Fukashi Horiuchi and Akio Higo,Nishiinomiya, and Hirosuke Yoshioka, Ikeda, Japan, assignors to SumitomoChemical Company, Limited, Higashi-ku, Osaka, Japan No Drawing. FiledDec. 29, 1972, Ser. No. 319,705 Claims priority, application Japan, Jan.7, 1972, 47 4,821 Int. Cl. C07c 61/04 US. Cl. 260514 H 4 Claims ABSTRACTOF THE DISCLOSURE )-Trans-chrysanthemic acid is effectively obtained bythe optical resolution of (:)-transor )-cis, transchrysanthemic acidusing ()-a-(1-naphthyl)-ethylam1ne.

The present invention relates to a process for producing(+)-trans-chrysanthemic acid represented by the formula I- Moreparticularly, the invention is concerned with a process for producing(+)-trans-chrysanthemic acid characterized by the optical resolution of(:)-trans-chrysanthemic acid or (i)-cis, trans-chrysanthemic acid withan optically active )-oz-( l-naphthyl)-ethylamine.

(-I- )-1R:3R-2,2-Dimethyl-3-isobutenyl-1,3transcyclopropane-l-carboxylic acid, commonly called(+)-transchrysanthemic acid, in the present invention constitutes theacid part of pyrethrins which occur in pyrethrum plants and are known tobe insecticidally active.

In recent years the problem of environmental pollution caused byagricultural chemicals has become a focus of adverse criticism. Amongsuch agricultural chemicals, insecticieds are in many cases used indoorsand therefore their low mammalian toxicity and their faciledecomposition to non-toxic substances are particularly demanded. In thisrespect, natural pyrethrins and their related synthetic insecticides,i.e. allethrin, phthalthrin, etc. have satisfactory properties and arewidely used at present. However, in the production of chrysanthemic acidin an industrial manner, it is inevitable that the acid is obtained as amixture of four acids, that is to say, cis and trans geometricalisomers, each including optical antipodes. When the esters of theseacids with :L- )-allethrolone as the alcoholic part are evaluated withtheir insecticidal potencies, the ester of (+)-trans-chrysanthemic acidis remarkably superior to others. Accordingly, the production of(+)-transchrysanthemic acid in an industrial manner has been studied asa very important problem. However, in spite of long years attempts atits technical development, any industrially advantageous process has notbeen found up to this time.

A known process for this purpose is that of Ishbel (J. Sir. Food Agric.,3, 189 (1952)). However, this process has such drawbacks that thedesired (+)-trans-chrysanthemic acid is obtained in low yields byrepeating the optical resolution operation twice and that quinine isused which is a naturally occurring alkaloid that is high-priced and itssupply is limited. There is also a known process using D-()-threo l paranitrophenol-Z-dimethylaminopropane-l,3-diol as an optical resolvingagent (French Pat. No. 1,536,485 specification). However, the use ofthis optically active amine is not economical from an industrialviewpoint. Also, the process by Ueda et a1. (Japanese patent publicationNo. 20,382/ 1971) is not satisfactory to obtain pure(+)-trans-chrysanthemic acid on an industrial scale. In the case ofusing L-lysine as the resolving agent (Japanese patent publication No.30,832/ 1971), the industrial practice of the process is accompaniedwith difiiculties in recovering and reusing the L- lysine.

As a result of long years intensive researches to overcome thesedisadvantages, the present inventors have found that(+)-trans-chrysanthemic acid can be obtained in high yield and in highpurity through simple operation by using an optically active amine whichis industrially available at low costs. The present invention has beenaccomplished on this finding.

Thus, the present invention is to provide a process for isolation of(+)-trans-chrysanthemic acid, which comprises dissolving (i-)-trans-, or-)-cis, trans-chrysanthemic acid in an organic solvent, adding(-)-oc-(1- naphthyl)-ethylamine to the solution, cooling the resultinghomogeneous solution to deposit crystals of the amine salt of(+)-trans-chrysanthemic acid, decomposing the salt by an acid or analkali, and recovering (-|-)-trans chrysanthemic acid.

The process of the present invention is illustrated in more detail asfollows.

One mol of (:)-trans-chrysanthemic acid or (:)-cis, trans-chrysanthemicacid is dissolved in a solvent and 0.5 to 1.5 mols of()-a-(1-naphthyl)-ethylamine is added thereto with stirring to form ahomogeneous solution. The solvent includes water, lower alkyl alcoholssuch as methanol, ethanol, n-propanol, iso-propanol, n-butanol,iso-butanol, sec.-butanol and tert.-butanol, ethers such as ethyl ether,isopropyl ether, butyl ether, dioxane and tetrahydrofuran, and aliphaticketones such as acetone and isobutylmethyl ketone, and a mixturethereof. To form a homogeneous solution, the mixture may be heated, ifnecessary. Thereafter, the solution is cooled to a temperature betweenabout 30 C. and room temperature, and the resulting crystals of theamine salt are collected by filtration.

The salt may be recrystallized from a suitable solvent to obtain thesalt of higher purity. The salt thus obtained is decomposed with an acidsuch as hydrochloric acid or sulfuric acid, etc. in the presence of anorganic solvent and then an organic layer and aqueous layer areseparated. The organic layer is washed with Water and concentrated underreduced pressure to obtain (i+)-trans-chrysanthemic acid. The aqueouslayer is rendered alkaline with an alkali, and the oily substance thusformed is extracted with an organic solvent. The organic layer is washedwith water and concentrated in vacuo to obtain ()-oc(1-naphthyl)-ethylamine. An alternative operation is as follows. The saltis decomposed with an alkali such as caustic soda etc. in the presenceof an organic solvent and then an organic layer and aqueous layer areseparated. The organic layer is washed with water and concentrated invacuo to recover ()-o-(l-naphthyl)-ethylamine. The aqueous layer isrendered acidic with an acid. The formed oily substance is extractedwith an organic solvent and the organic layer is washed with Water andconcentrated in vacuo to obtain (!+)-trans-chrysanthemic acid. Thus,optically active (+)-trans-chrysanthemic acid is obtained by the simpleoperation and recovery of the optically active amine is accomplished ina quantitative yield.

As is clear from the above illustration it is possible to obtain thedesired (+)-trans-chrysanthemic acid alone from a mixture of (i)-cis and(i)-trans-chrysanthemic acids in high purity and in high yield and theresolution reagent amine can be very easily recovered with high yield.Thus, the process of the present invention is an extremely excellenttechnique in these points.

3 The process of the present invention is explained in more detail withreference to the following examples, which are only illustrative but notlimitative.

EXAMPLE 1 16.8 g. of (i)-transchrysanthemic acid was dissolved in 120ml. of anhydrous ethanol and 17.1 g. of ()OL- (1-naphthyl)-ethylaminewas added to the solution. The solution was allowed to stand in arefrigerator. Thereafter, the crystals were collected by filtration. Thecrystals were then recrystallized from 60 ml. of anhydrous ethanol toobtain 10.7 g. of white crystals, m.p.-=144.5-145.5 C.; [a] =19.90(dimethyl sulfoxide). The crystals Were dissolved in a aqueous causticsoda solution. The oily layer was extracted with ether and 5.2 g. of()-oc-( lnaphthyl)-ethylamine was recovered. The aqueous layer wasacidified with hydrochloric acid and extracted with ether to obtain 5.2g. of (+)-trans-chrysanthemic acid. Yield=62%; [a] =i-]14.6 (ethanol).Also, 11.1 g. of the amine was recovered from the ethanol mother liquid.

EXAMPLE 2 A mixture consisting of 16.8 of (i)-trans-chrysanthemic acidand 1.5 g. of i-cis-chrysanthemic acid was dissolved in 120 ml. ofanhydrous ethanol and 17.1 g. of (-)-oz-( l-naphthyD-ethylamine wasadded to the solution. Thereafter, the same treatment was carried out asin Example 1 and 5.1 g. of ([+)-trans-chrysanthemic acid was obtained.[a] 14.5 (ethanol). By gas chromatographic analysis, this product wasfound to contain less than 1% of the cis acid.

EXAMPLE 3 A mixture of 16.8 g. of (:)-trans-chrysanthemic acid and 17.1g. of (,)-cc-( l-naphthyD-ethylamine was dissolved in 120 ml. of 95%hydrous ethanol under heating. The solution was allowed to cool to 25 C.and kept for 2 hours at the same temperature while being stirred. Thecrystals were collected by filtration to obtain the crude salt. Thecrude salt was recrystallized from said ethanol to give 9.2 g. of whitecrystals, m.p. 145 to 146 C. The crystals were treated according to theprocedure similar to that of Example 1 to obtain 4.3 g. of,+)-trans-chrysanthemic acid, yield 51.2%, [u] .=+l4.8 (ethanol).

EXAMPLE 4 Example 3 was repeated except that isopropyl etherethanol(2:1) was used in place of hydrous ethanol, whereby 12.2 g. of whitecrystals, m.p. 145 to 147.5 C. were obtained. The crystals were treatedaccording to the procedure similar to that of Example 1 to give 5.8 g.of trans chrysanthemic acid, yield 69.0%,

4 EXAMPLE 5 Example 4 was repeated except that a mixture of (i)-trans,(i)cis- (88:12) chrysanthemic acids was treated in place of)-trans-chrysanthemic acid, whereby 10.7 g. of white crystals, m.p. to146 C., were obtained. The crystals were treated according to theprocedure similar to that of Example 1 to obtain 5.1 g. of(;+)-transchrysanthemic acid, yield 69%, [a] =l+ 14.6 (ethanol). By gaschromatographic analysis, this product was found to contain less than 1%of the cis acid.

EXAMPLE 6 Example 3 was repeated except that acetone was used in placeof hydrous ethanol, whereby 12.4 g. of white crystals, m.p. 144 to 145C., were obtained. The crystals were treated according to the proceduresimilar to that of Example 1, to obtain 5.9 g. of(+)-trans-chrysanthemic acid, yield 70.2%, [a] =:+14.5 (ethanol).

What is claimed is:

1. A process for isolation of (+)-trans-chrysanthemic acid, whichcomprises dissolving (i)-trans-chrysanthemic acid or (j;)-cis,trans-chrysanthemic acid in a solvent selected from the group consistingof water, lower alkyl alcohols, lower alkyl ethers, dioxane,tetrahydrofuran, lower alkyl ketones and a mixture thereof, adding()-oc- (1-naphthyl)-ethylamine to the solution, cooling the resultinghomogeneous solution to deposit crystals of the amine salt of(+)-trans-chrysanthemic acid, decomposing the salt by an acid or analkali, and recovering trans-chrysanthemic acid.

2. The process according to claim 1, wherein the amount of()-a-(1-naphthyl)-ethylamine is 0.5 to 1.5 mols per mol of(i)-trans-chrysanthemic acid or (i)- cis, trans-chrysanthemic acid.

3. The process according to claim 1, wherein the homogeneous solution iscooled to a temperature between about 30 C. and room temperature.

4. A process according to claim 1, wherein the solvent is water, a loweralkyl alcohol, ethyl ether, isopropyl ether, butyl ether,tetrahydrofuran, acetone, or isobutyl methyl ketone.

References Cited UNITED STATES PATENTS 8/1961 Bottoms 260-5708 6/1973Ueda et al 260-514 H

1. A PROCESS FOR ISOLATION OF (+) TRANS-CHRYSANTHEMIC ACID WHICHCOMPRISES DISSOLVING ($)-TRANS-CHRYSANTHEMIC ACID OR ($)-CIS,TRANS-CHRYSANTHEMIC ACID IN A SOLVENT SELECTED FRON THE GROUP CONSISTINGOF WATER, LOWER ALKYL ALCOHOLS, LOWER ALKYL ETHERS, DIOXANE,TETRAHYDROFURAN, LOWER ALKYL KETONES AND A MIXTURE THEREOF, ADING(-)-A(1-NAPHTHYL)-ETHYLAMINE TO THE SOLUTION, COOLING THE RESULTINGHOMOGENEOUS SOLUTION TO DEPOSIT CRYSTALS OF THE AMINE SALT OF(+)-TRANS-CHRYSANTHEMIC ACID, DECOMPOSING THE SALT BY AN ACID OR ANALKALI, AND RECOVERRING (+)TRANS-CHRYSANTHEMIC ACID.